Cancer is the leading cause of death in our current canine pet population. Previous studies have found that 45% of dogs aged 10 years or older, and 23% of dogs of any age, die from different types of cancer.
Recent reports indicate that there are over 74 million dogs in the USA. The estimated cancer incidence rate in dogs in the USA is 243-381/100,000 which is similar to humans, and many of these dogs will be treated with currently available standard chemotherapy protocols. However, chemotherapeutics have significant side effects principally as a result of their actions on non-cancerous tissues and cells. Furthermore, most of these treatments have poor overall efficacy and cancer remains the leading cause of death in the canine pet population. Alternative therapies that specifically target chemotherapeutics to the cancer cells and so increase their efficacy and reduce off-target side effects are needed.
The mainstay of cancer therapy in veterinary medicine is the systemic administration of a combination of chemotherapeutic agents that inhibit cell division and induce cell death. These agents however are not tumor-specific and frequently cause adverse side affects which limit the dose that can be given and the therapeutic efficacy of the agent.
Recent efforts in human cancer therapy have focused on the use of monoclonal antibodies such as trastuzumab (anti-erb2), rituximab (anti-CD20) and bevacizumab (anti-Vascular Endothelial Growth Factor) that directly target tumors and their vasculature providing a specific anti-tumor response that has shown promising results in phase II/III clinical trials. However, the xenogeneic nature of these reagents and the lack of known tumor-associated antigens (TAA) limits their use in the dog.
The use of antibodies and antibody fragments (scFv) that specifically target malignant cells have revolutionized the treatment of certain cancers in humans. Currently, tumor-specific scFvs are being evaluated alone, coupled to cytotoxic agents or expressed in re-directed tumor-specific T cells for the targeted treatment of primary and metastatic cancer in people. Until now, these exciting advances in the targeted therapy of cancer have not been possible in canine cancer patients since monoclonal antibodies or scFvs of canine origin have not been developed, canine TAA have not been identified and in many cases xenogeneic antibodies don't cross react with canine antigens or their efficacy is limited by the development of neutralizing antibody responses.
It would therefore be desirable to have a way of treating cancer in dogs that could be administered systemically and repeatedly if necessary, and that specifically targets cytotoxic agents to malignant cells, thereby reducing the adverse side effects of chemotherapies and improving therapeutic efficacy. In addition, antibody fragments that recognize and neutralize pathogens such as viruses and bacteria also represent a targeted approach to the treatment of infectious disease. Furthermore, antibody fragments that can specifically recognize and neutralize cytokines and other soluble proteins may represent a novel approach to the treatment of infectious and inflammatory diseases.